On January 8, 2010, Thomas released a statement through the University of Texas which announced his decision to forgo his remaining eligibility and enter the 2010 NFL Draft. He attended the NFL Scouting Combine in Indianapolis and completed the majority of drills, but chose to skip the short shuttle and three-cone drill. On March 31, 2010, he participated at Texas' pro day and improved his 40-yard dash (4.37s), 20-yard dash (2.47s), and 10-yard dash (1.49s). Thomas sustained a hamstring injury during his workout and was unable to complete his entire performance.
The Seattle Seahawks selected Thomas in the first round (14th overall) of the 2010 NFL Draft. Thomas was the second safety drafted in 2010, behind Eric Berry. At age 20, he was one of the youngest players eligible for the draft.
On July 31, 2010, the Seattle Seahawks signed Thomas to a five-year, $18.30 million contract that includes $11.75 million guaranteed and a signing bonus of $500,000.
Head coach Pete Carroll named Thomas the starting free safety to begin the regular season, alongside strong safety Lawyer Milloy. He made his professional regular season debut and first career start in the Seattle Seahawks' season-opener against the San Francisco 49ers and recorded seven combined tackles in their 31–6 victory. On September 26, 2010, Thomas made six combined tackles, two pass deflections, and two interceptions during a 27–20 victory against the San Diego Chargers in Week 3. Thomas made his first career interception off a pass by Chargers' quarterback Philip Rivers, that was originally intended for tight end Antonio Gates, and returned it for a 34-yard gain in the fourth quarter. On November 14, 2010, he collected a season-high eight solo tackles in the Seahawks' 36–18 victory at the Arizona Cardinals in Week 10. In Week 12, Thomas collected eight combined tackles and returned a blocked punt for the first touchdown of his career during a 42–24 loss to the Kansas City Chiefs. Thomas recovered a blocked punt that Kennard Cox blocked by Dustin Colquitt and returned it for a ten-yard touchdown in the first quarter. Thomas started all 16 games during his rookie season in 2010 and recorded 76 combined tackles (64 solo), seven pass deflections, five interceptions, and a forced fumble.