Morgan devoted the prime-time show's final minutes Friday night to the issue that he said has been a "consistent and often very controversial" part of "Piers Morgan Live."
The British-born host cited gun violence statistics and expressed dismay that mass shootings including those in Newtown, Conn., and Aurora, Colo., haven't led to stricter laws.
Morgan blamed politicians that he said had been bullied into "cowardly" silence by a gun lobby led by the National Rifle Association.
A message seeking comment from the NRA was left Friday night with an answering service at its headquarters.
Piers concluded with remarks addressed to his critics.
"To those who claim my gun control campaign has been anti-American, well, the reverse is true. I'm so pro-American I want more of you to stay alive," he said, adding, "Now it's down to you."
Morgan is a former U.K. tabloid editor who reinvented himself as a TV personality with stints as a judge on "Britain's Got Talent" and its U.S. spinoff, NBC's "America's Got Talent," and as a contestant on "Celebrity Apprentice."
In 2011, he succeeded longtime CNN host Larry King in the 9 p.m. Eastern time slot, but drew increasingly paltry ratings. He has said that CNN's audience tired of hearing a Brit weigh in American cultural issues.
Last fall, the already struggling "Piers Morgan Live" faced increased competition from a revised Fox News Channel lineup that included a strong new performer opposite Morgan with Megyn Kelly's "The Kelly File."
When the show's end was announced last month, Morgan said he was in discussions with CNN regarding a new role. The channel said then that his future was undetermined.
Morgan served as editor of The Daily Mirror from 1995 to 2004. He has been questioned in connection with Britain's long-running phone hacking scandal, which has led to numerous arrests, resignations and the closure of Rupert Murdoch's News of the World tabloid.
In February, Morgan confirmed that he was interviewed in December by British police investigating the illegal interception of telephone voicemails. Morgan, who said he had given a previous witness statement, has consistently denied wrongdoing.