Murphy, 28, fended off a furious late challenge from 19-year-old Keaton Jones, winning in 1min 54.33sec as Jones clocked 1:54.61 to deny Jack Aikens, who was also squeezed out of the top two in the 100m back won by Murphy.
Regan Smith and Kate Douglass will also be doubling up in Paris after posting their second wins of the week at Lucas Oil Stadium, home of the NFL's Indianapolis Colts.
Murphy, who won double backstroke gold in Rio de Janeiro in 2016 but settled for silver and bronze in Tokyo, became the first man to sweep the 100m and 200m backstrokes at three straight US Olympic trials.
It's a remarkable trials first in a country whose swimming history includes backstroke greats Lenny Krayzelburg and Aaron Peirsol.
"There's a lot of guys that have come before me," Murphy said. "I had posters of them on my wall. I'm never going to view myself as better than them and there's definitely more work to do, but I'll take this one in and be happy about it."
Smith, fresh off a world record in the 100m backstroke final on Tuesday, expanded her Paris programme with a victory in the 200m butterfly in 2min 05.70sec.
Second at the final turn behind Alex Shackell, Smith dug deep to slip past the 17-year-old, who booked her first trip to the Olympics with a runner-up finish in 2:06.69.
It was just the start of a busy night for Smith, who returned less than 45 minutes later to top the times in the 200m backstroke semi-finals.
Shackell's first Olympics will be a family affair. Her 19-year-old brother Aaron won the 400m free on Saturday to punch his Olympic ticket. Their father, Nick Shackell, swam for Great Britain at the 1996 Olympics.
Douglass set a trials record of 2:19.46 to win the 200m breaststroke, leading wire to wire to capture another victory a day after her 100m freestyle triumph.
"I'm really happy with both of those wins I've had so far," said Douglass, who admitted that when she arrived for trials and saw a giant poster of herself plastered on the front of the massive stadium -- where crowds for finals sessions top 20,000 -- it was a bit unnerving.
"Definitely was a little scary at first," she said. "I felt the pressure after seeing that, but I feel like I've done a good job of handling it and this crowd has really helped me push myself to achieve my goals for the meet."
Dressel into 50m free final
Behind her, 100m breaststroke winner Lilly King and Alex Walsh were dueling for second, King's storming final lap taking her past Walsh in the final meters for second in 2:21.93.
That wasn't the only excitement of the night for King, whose boyfriend proposed to her moments after the race.
Caeleb Dressel, who won't defend his 100m free title after a third-place finish on Wednesday relegated him to relay duty, bounced back with the second-fastest time in the semi-finals of the 50m free.
Chris Guiliano, the 100m free winner, was fastest in 21.59sec with Dressel, winner of five gold medals at the Tokyo Games, winning his semi in 21.61 as he vies to return to the top of the sport after stepping away in 2022.
There was an extended battle for the last spot in the final, after Adam Chaney and Jonny Kulow tied for eighth-fastest in the semis.
Both touched in 21.79 in the first swim-off -- a tenth of a second faster than they swam in the semi-finals.
A second swim-off saw Chaney grab the final berth in 21.81, Kulow clocking 21.99.
