Thompson and countryman Daniel Summerhays stood on 17-under 199 after 54 holes with fellow Americans Chad Campbell, Woody Austin, Kyle Reifers and Cameron Beckman sharing third on 201.
Thompson was among the players who awoke early to finish the storm-interrupted second round Saturday morning before playing the third in the afternoon.
"It was a long day but I got a nice little gap in between," Thompson said. "I'm just scoring a little bit better and better."
Lightning returned to halt play as the final group reached the 18th green, with Summerhays having a 19-foot birdie putt to match Thompson for the lead.
After waiting nearly an hour for the chance, Summerhays returned to the green and rolled in the putt for a share of the lead in his bid for his first US PGA title.
The tournament allows players who did not qualify for the British Open, being played in Scotland, to compete for a crown while top players are at the year's third major event.
Thompson opened with his lone bogey of the round but ran off two runs of three birdies in a row, the first starting at the par-four fourth and the second ending at the par-fifth 11th. He added a birdie at the 14th and a two-foot birdie putt at the par-five 18th.
Thompson, whose best tour showing was a runner-up effort at the 2008 Ginn dur Mer Classic, is in contention on the same weekend sister Lexi is in the final group in quest of an LPGA title.
If Nicholas can win, the Thompsons would join Billy Kratzert and sister Cathy Gehring and siblings Jim Gallagher and Jackie Gallagher-Smith as the only brother-sister winners on the PGA and LPGA tours.
"Hopefully it's a great day for the Thompson family," he said. "Whatever happens, it's a great day for both of us to be in contention."
Campbell, who played 31 holes in all on Saturday, has four career US PGA titles but none since the 2007 Viking Classic. The 2003 Tour Championship winner's best showing this season was a share of 15th at last week's John Deere Classic.
"The last month I've started playing a little bit better golf, doing the things I need to do to get into contention," said Campbell. "I'm glad to be in position to challenge tomorrow."
Beckman, who won this event in 2001, has not won since 2010 in the US PGA's Mexico stop but is confident after making his first cut in six tries this season.
"I'm really happy," he said.
"I've spent the last three months working a lot harder than I had in the last two years. I think I've been working on the right stuff."
Austin, who played 30 holes Saturday, went over the 18th green and needed two chips to reach the putting surface on his way to a bogey on the hole that has played the easiest this week.
"Normally I would say I'm very happy but to finish the way I did was very disappointing," Austin said. "It's going to be hard to get the taste out of that last hole out of my mouth for a while. A lot of guys are going to shoot low tomorrow and I didn't need to throw away two shots."
Austin, 49, seeks his first US PGA title since 2007.
Scores after the third round of the $3 million US PGA Sanderson Farms Championship (USA unless stated, par 72):
199 - Nicholas Thompson 69-65-65, Daniel Summerhays 63-67-69
201 - Chad Campbell 67-69-65, Cameron Beckman 72-64-65, Woody Austin 69-65-67, Kyle Reifers 65-69-67
202 - Brendon Todd 72-64-66, Bill Lunde 67-67-68, Vaughn Taylor 67-67-68
203 - Rory Sabbatini (RSA) 68-68-67, Jim Herman 66-69-68
204 - Matt Every 71-67-66, Noh Seung-Yul (KOR) 69-68-67, Chris Kirk 69-65-70, Paul Stankowski 66-68-70, Troy Matteson 67-67-70
205 - Will Claxton 66-71-68, Kevin Sutherland 70-69-66, Brad Fritsch (CAN) 66-69-70, Jonathan Randolph 66-69-70, Billy Mayfair 72-62-71, Fabian Gomez (ARG) 70-64-71
206 - Greg Chalmers (AUS) 70-69-67, Billy Andrade 73-66-67, Scott Langley 70-69-67, Ken Looper 68-69-69, Martin Flores 71-65-70, William McGirt 66-70-70, Peter Lonard (AUS) 67-67-72