She beat Dale Creasy Jr., Jeff Arend and Tommy Johnson Jr. to reach the final.
"All day I was just trying not to think about it," Force said.
In the final, Pedregon's Toyota Camry slowed near the finish in a 4.225 at 250.60.
"I grew up watching my dad battle with Cruz and there he was lined up in the lane next to me," Force said. "My nerves were really going. I screwed up trying to get the car staged. Luckily, I got it together."
Ashley Force Hood, Courtney's older sister, was the first female Funny Car winner in 2008.
"To start with when Brittany and Courtney both went to No. 1 I know this was already a special weekend," Force Hood said. "I thought it could be a really good race for both of them since their race cars were running so well. They were both going rounds today and I started to get excited because sometimes you just have the magic. I had a feeling that maybe this would be the day. It is pretty cool. I watched it on my computer with Autumn, Jacob and Noah. I actually made a video. The kids were jumping up and down we were all really excited."
Spencer Massey won in Top Fuel, and Allen Johnson in Pro Stock.
Massey raced to his second victory in a row and second at Topeka, beating defending series champion Shawn Langdon in the final with a 3.871 at 314.02.
Massey topped Brittany Force in the semifinals.
Johnson won for the third time this season and the third time at Topeka, outrunning teammate Jeg Coughlin in the final. Johnson powered his Dodge Dart to a 6.663 at 207.81.