Darvish said through his interpreter Tuesday that he knew he wasn't going to be ready to pitch in the opener at home against Philadelphia because of neck stiffness.
The announcement came a day after Darvish stopped throwing while playing catch.
Darvish was initially scratched from starting a minor league spring training game Friday. He said then that he had stiffness in his neck that he felt after waking up one morning, and repeated again Tuesday that the problem was from sleeping wrong.
Darvish is scheduled to return to Texas to be examined by spine and back specialist Dr. Drew Dossett.
The Rangers will then determine what to do next, including the possibility of Darvish going on the disabled list. A DL move could be backdated and allow him to be eligible for a return only a week into the season.
It was the third day in the row the Rangers got significantly bad injury news.
On Sunday, the team found out prized prospect and expected everyday second baseman Jurickson Profar will miss 10 to 12 weeks with a muscle tear in his right shoulder. Then it was announced Monday that catcher Geovany Soto is expected out about the same amount of time with a muscle tear in his right knee.
The Rangers, who last season missed the playoffs for the first time in four years, already knew they would be starting the season without left-handers Matt Harrison (back) and Derek Holland (microfracture knee surgery) in the rotation. Harrison could be back by mid-April.
Darvish is going into his third major league season after being a standout in Japan. He started the second game for the Rangers last season, when he came within one out of a perfect game against Houston. He went on to finish 13-9 and lead the majors with 277 strikeouts, finishing second in the AL Cy Young Award voting.
Darvish is 29-18 with a 3.34 ERA in his 61 games with the Rangers over the past two seasons, and his 498 strikeouts are the most in the majors during that span. The right-hander last year became the first pitcher since Orel Hershiser in 1989 to suffer four 1-0 losses in the same season.
The Rangers didn't immediately say who would replace Darvish as the starter Monday opposite Cliff Lee and the Phillies.
Really, the only other two pitchers who had been set in the rotation with Darvish are 22-year-old left-hander Martin Perez, who was 10-6 as a rookie last season, and converted hard-throwing setup man Tanner Scheppers.