Booth goes missing six months after he and Brennan left their careers behind, but a case with ties to the couple pulls Brennan back into the world of forensic analysis, which brings her into contact with a member of Booth's family and Arastoo Vaziri, who's taken the lead at the Jeffersonian in her absence. Meanwhile, the FBI investigate Booth's disappearance, but one agent's tactics are bad for the team's morale.

Booth is still missing, but the team learns that Agent Miller has hidden information about his whereabouts and physical state. Meanwhile, a digital forensic scientist helps Angela try to decipher information pertaining to Booth's location and the circumstances of his disappearance; and Arastoo makes a decision that will change his and Cam's personal and professional relationships.

On Brennan and Booth’s first official day back at their respective positions at the Jeffersonian and the FBI, things get exciting when remains are found at a fish farm under suspicious conditions, prompting them to investigate. After it’s discovered that someone harvested several of the victim’s internal organs before he was dumped in the water, Angela tracks down the seller and buyer of the organs to try to uncover important details in the case. Meanwhile, Booth readjusts to his position back at the FBI and discovers Aubrey has taken over his old office; Hodgins pushes Angela to showcase her photography work; and Cam struggles with her decision to choose work over her relationship with Arastoo.

When remains of real estate agent Justin Ross are discovered in a forest and appear to have been destroyed by coyote-wolf hybrids, Brennan enlists the help of fellow brilliant forensic anthropologist Dr. Beth Mayer to assist in the investigation. In addition to her professional achievements, Mayer is surprisingly knowledgeable about the world of fantasy football, a key link to Ross’ past and one that could provide vital information in finding his killer. As Booth and Aubrey dig into Ross’ fantasy football league history, they discover he was actively involved in a Twitter feud with NFL star Lou Divers, and was also owed a large sum of money from the league’s commissioner, making each of them suspects. Meanwhile, Brennan resists feeling competitive as Mayer impresses the team with her expertise and decades of accomplishments.

It’s Halloween time at The Jeffersonian as the team gets a surprise visit from Lt. Abbie Mills and Ichabod Crane, who have traveled from the spooky town of Sleepy Hollow to help on a murder case of a young woman whose body is found on top of a 18th century military general’s headless body. The new foursome must figure out how to work together to discover who the 200-year-old headless corpse is and how the two murders are linked. Meanwhile, Booth and Brennan come up with the ultimate Halloween pranks to play on each other.

The crossover continues on Sleepy Hollow S03E05 Dead Men Tell No Tales (II).

A pair of funny sanitation workers discover the shredded body of a U.S. Senator in a street sweeper, which leads Brennan, Booth and the team to Capitol Hill, where they meet with U.S. Senator and majority whip Hayley Winters and the victim's chief of staff Eric Morales to get to the bottom of this political murder. Meanwhile, as Aubrey starts to develop a relationship with squintern Jessica, he looks into her past to make sure nothing will harm his dream of a future in politics

The team investigates the high-stakes murder of a political journalist who was found dead after recently publishing an article exposing corruption in the NSA. Due to the nature of the investigation, Hodgins’ paranoia takes over as the team realizes their every move is being watched. Meanwhile, Brennan secretly tries to plan a surprise for Booth and the whole team celebrates Thanksgiving together.

Booth and Brennan go under cover at an Old West-style shooting competition; Angela and Hodgins talk about the future; Cam and Sebastian grow closer.

The team investigates a police officer's murder and decides what is important to their futures.

Hodgins is eight weeks into his rehabilitation for his paralysis and forced to navigate life in a wheelchair. Meanwhile, Brennan and Booth investigate the death of a public defender who had multiple defendants from previous cases with motives to kill her.

The team investigates a body found in a car crash, the remains of which belong to a founder of a men's rights organization who may have been the victim of domestic abuse. As Brennan learns more about the tenets of the victim's organization, which claims middle-aged white men are oppressed and feminists are man-haters, Brennan uncharacteristically loses her cool during an interrogation and assaults the organization's co-founder. Meanwhile, Angela and the team struggle to deal with Hodgins post-wheelchair bitterness and Booth is convinced Brennan is a jinx for the Philadelphia Flyers.

The Jeffersonian investigates the decomposing body of a social worker in the park, but evidence suggests the killer lived with the body for months before dumping it. Things get even more complicated when they determine another set of remains has similar details, which link the victims to a serial murderer who had sinister interactions with his victims' bodies. Booth and Aubrey consult with behavioral analyst Karen Delfs to help with clues to the killer's identity, while Cam tries to determine what (and who) she wants in her romantic life.

The Jeffersonian investigates the murder of a convicted felon who had been released to a halfway house, but disappeared, and a suspect in the case has ties to Booth. Meanwhile, Brennan testifies at an FBI hearing about the circumstances regarding her assault of an unarmed suspect from a previous case, and the outcome of the hearing could lead to her suspension and prevent her from working with the FBI. Aubrey and Jessica’s first kiss is delayed again and Hodgins continues to push Angela away.

The team investigates the body of a private investigator who was found frozen in ice, after being dumped in the Potomac. The victim, a man with many enemies, was a "fixer" who made sure his clients' problems got "resolved." Meanwhile, Aubrey is shocked to find information tied to his father's whereabouts, Angela and Hodgins continue to work on their rocky relationship, Brennan and Booth get Christine's first report card and criminal behaviorist Karen Delfs asks Aubrey out on a date.

The team investigates the death of the leader of the Lynwood University male acapella singing group, "The Whippersnaps," whose body was found in the school rat lab. The victim recently kicked out Ian Jansen, one of the group's best singers, sending Booth and Aubrey to question Ian and other current members of the male group and some stars of the competing female acapella group to get a handle on the group dynamics and what could have led to the murder of one of their own. Meanwhile, surprising information about Aubrey's own college experience is brought to light, Hodgins applies for an experimental nerve regeneration study, Booth tries to plan a summer trip with Parker and a new intern joins the Jeffersonian lab.

A drunk college student discovers the dead body of a Secret Service agent just before a presidential visit to the area. Booth is ready to hit the ground running and turns to Secret Service agent and former colleague Brandt Walker for information, but is surprised to learn the Secret Service has reservations about Booth’s involvement in the case. The team uncovers some shocking evidence that heightens the seriousness of the case, causing Booth to step up for his country. Meanwhile, Brennan is out sick with the flu and former intern Dr. Colin Fisher returns to the Jeffersonian to run lead on the case, but Brennan refuses to be kept out of the loop. Also, Hodgins takes his life into his own hands and turns a corner after a potentially dangerous experiment.

To produce a television segment on the Jeffersonian’s Medico-Legal lab, a documentary crew follows Brennan, Booth and the Jeffersonian/FBI team on a “typical” case as they investigate a corpse found in a landfill that was buried there more than a decade ago. The camera captures normally unseen footage of the team at work, while candid commentary by each of the team members provides an inside look at the investigation as Booth and Aubrey show off their unique skills in the field, and Brennan and her team prove their expertise and integral importance to solving murder cases.

The team investigates the death of a popular professional hockey player whose headless corpse was dumped in the river. As Booth and Aubrey question the player's coach, Booth's depth of hockey knowledge is integral to solving the case, and he's reunited with a hockey rival from his past, putting him back on the ice once again to face off against him. Meanwhile, Hodgins and Oliver have a competition of their own when Hodgins builds two drones and they compete to retrieve the victim's missing head, and Booth and Brennan attempt to declutter their home.

When the remains of famous billionaire explorer Henry Charles are found in Antarctica, the high profile case is brought to Brennan and Booth to determine if his death was a murder. The Jeffersonian team confirms he was killed when he went missing ten years ago on an expedition, but the timeframe puts the Jeffersonian's Dr. Clark Edison, who was with Charles for the expedition, on the short list of suspects. Meanwhile, Cam's sister comes into town to help with wedding plans and old family friction comes into the picture.

The team investigates a body found at a glass recycling plant with a diamond lodged in its jaw. French Inspector Rousseau approaches the team with an accusation against the Marquis De Chaussin, who is revealed to be the victim's husband and lives in Virginia. Meanwhile, Booth discovers he suffers from a temporary eye illness, and Hodgins thinks he's being followed by a ghost.

The team dives back into investigating a serial killer from the past, attempting to find “The Puppeteer,” who lives with his victims’ bodies before disposing of them. Meanwhile, Brennan works through her guilt over her retirement last year, blaming herself for not stopping the serial killer earlier. However, little does she know she might be in some trouble of her own.