Mike Rowe was originally meant to be the on-camera host of Deadliest Catch and appeared in taped footage as himself during the first season. However, when Discovery greenlit Dirty Jobs, Rowe was required to choose only one show to appear on camera, so most of his season-one footage ended up in the show's 'Behind the Scenes' episode instead, and he became the off-camera narrator.

A two-person TV crew lives on each profiled boat, shooting with handheld Sony HVR-Z5U and HVR-Z7U HDV cameras, supplemented by four permanently mounted stationary cameras, a chase boat (the F/V Time Bandit served as the main chase boat in season 1), underwater cameras (including a 'crab's eye view' camera attached to a crab pot from season 2), and a submersible-mounted camera from season 3.

Starting with the Season 9 'Behind the Lens' special, filming used a helicopter with a belly-mounted turret camera, the same type of camera rig used to film scenes in the James Bond film Skyfall.

Camera crews faced real danger on set: Captain Sig Hansen said he once screamed at a cameraman to move out of the way just seconds before a 900-pound crab pot swung across the spot where he was standing, saving his life. In another incident, a distracted cameraman fell through an open deck hatch and broke three ribs, then had to buy the crew a case of beer per crab-boat tradition.

During a season 4 episode, Wizard captain Keith Colburn demanded the cameras be turned off during a heated argument with his brother Monte, but the Colburns forgot to remove their wireless microphones, so the audio of their exchange was recorded and aired anyway.

On September 28, 2010, it was reported that captains Andy and Johnathan Hillstrand and Sig Hansen would not return to the show due to litigation initiated by Discovery Communications against the Hillstrands; the dispute was resolved and all three returned for season 7.

During the filming of season 6, Captain Phil Harris suffered a stroke and collapsed in his stateroom; producer Thom Beers said Harris insisted the camera crews keep filming him so audiences could see the full story of family bonds, and filming continued through his airlift to Anchorage for emergency brain surgery. Harris died 11 days later, on February 9, 2010, and the episode covering his death, 'Redemption Day', drew a record 8.5 million viewers, becoming the third-most-watched broadcast in Discovery Channel history at the time.

After the first season, the show adopted Bon Jovi's 'Wanted Dead or Alive' as its main theme song, which was gradually truncated over the years before being replaced entirely after season 11.

The series grew out of two earlier Discovery Channel pilots produced by Thom Beers: the 1999 one-hour documentary 'Deadliest Job in the World' and the 2004 three-part miniseries 'America's Deadliest Season'; Beers himself provided narration for both before handing the role to Mike Rowe when the regular series was ordered.

A 2013 episode of MythBusters featured captains Johnathan Hillstrand and Scott Campbell Jr. traveling to M5 Industries to test three myths related to crab fishing, including whether crab pots are impervious to explosives.