Yankey, a consensus All-American, and Fleming are two of the three Stanford players with eligibility remaining who will forgo their final season for a chance to play professionally.
Stanford safety Ed Reynolds is also throwing his name into the draft pool. The deadline for such actions was Wednesday.
Linebacker A.J. Tarpley and defensive end Henry Anderson announced they will return to school to finish their eligibility.
Yankey is the eighth unanimous All-American at Stanford, having been named to every major All-America team at left guard in 2013. In 2012, he was a consensus selection at left tackle.
"I reached my decision following conversations with family and coaches, and am greatly looking forward to the next chapter in life," Yankey said. "The decision was not easy. I have loved my time at Stanford and am a proud member of Nerd Nation. I am humbled at the prospect of joining a long list of Stanford alumni currently playing in the NFL."
The active list of NFL players from Stanford currently stands at 27, with several other Cardinal players set for the draft, including fellow All-Americans Trent Murphy, Shayne Skov and Tyler Gaffney.
The Stanford offensive line, called for three holding calls all year, ranked seventh nationally for fewest tackles for loss allowed per game (4.14) and 11th nationally for fewest sacks allowed per game (1.14).
Yankey and Fleming opened plenty of gaps for Gaffney to rush for over 100 yards in nine games.
"I want to thank my coaches, teammates and the Stanford family for a spectacular four years at a wonderful university," Fleming said. "I would also like to give special thanks to the professors in the aeronautics and astronautics department."
Fleming is on pace to graduate with a degree in aeronautics and astronautics this spring.
Reynolds, an All-America, said he will re-enroll to Stanford for the spring quarter and return again during the offseason to complete work toward his degree in political science.
"After much thought and discussion with my family and mentors, I have decided to enter the NFL Draft," Reynolds said. "I would to thank the Stanford football family for putting me in this position and preparing me for the next level. A very special thanks to our coaching staff, support staff and my teammates for making the memories of these past four years last a lifetime."
Reynolds was third among Stanford defenders in 2013 with 87 tackles, adding four breakups, five passes defended and one interception. He was a pivotal cog in a defensive unit that ranked third nationally in rushing defense (89.4 yards per game), seventh in tackles for loss (7.8 per game) and 16th in total defense (343.1 yards per game).
As a junior in 2012, Reynolds had a team-high six interceptions, the most by a Stanford player since Jim Kaffen's seven in 1973. He had a school-record three interceptions returned for a touchdown and ranked first nationally with 301 interception return yards, one yard short of NCAA single-season record.
Yankey is on track to graduate this spring with a degree in science, technology and society.
"I want to thank everyone at Stanford for their unwavering support throughout my four years," Yankey said. "Coming here was an incredible opportunity and everyone on campus — from professors and coaches to support staff and fans — have demonstrated why this place is so special."
This season, Stanford became the first team since Oklahoma in 2003 with a consensus All-American on offense, defense (Murphy) and at kick returner (Ty Montgomery).
Stanford (11-3 overall, 7-2 Pac-12) enjoyed a fourth consecutive BCS appearance to complete the year.
The Cardinal finished the season ranked 11th in the final AP poll, following its 24-20 setback against No. 3 Michigan State on Jan. 1 in the 100th Rose Bowl Game.