He is best remembered as anchor of the ABC Evening News from 1968 to 1970 and later as Washington D.C.-based co-anchor of World News Tonight from 1978 to 1983. During the Iran hostage crisis, he began the 30-minute late night program America Held Hostage, which later was renamed Nightline.
Reynolds was also the original anchor of "America Held Hostage", a series of special reports seen weeknights at 11:30 p.m./10:30 Central on the Iran hostage crisis in November 1979 that evolved into the newsmagazine Nightline in 1980. Shortly after the special reports began, Reynolds was replaced by Ted Koppel.
One supposedly infamous moment in Frank Reynolds' career occurred on March 30, 1981 during live news coverage of the assassination attempt on U.S. President Ronald Reagan. White House Press Secretary James Brady, a close friend of Reynolds, had been erroneously reported by all three networks as having died from the head wound he suffered in the incident, and, further, they reported that Reagan had not been struck at all. Upon learning that the information was incorrect, Reynolds suddenly appeared noticeably upset and, looking around at staffers in the background, angrily burst out:
"Let's get it NAILED DOWN...somebody...let's find out! Let's get it straight so we can report this thing accurately!"
The network quickly moved to a break and upon return, Ted Koppel was seated next to Reynolds to share anchor duties and, perhaps, be a calming influence on his clearly agitated co-worker. It was one of the few times in television history that viewers witnessed an otherwise professional veteran anchor become angry on air. Reynolds nonetheless emerged from the incident with his reputation unscathed.
Reynolds died from bone cancer at the age of 59, which was discovered while he was being treated for acute hepatitis in the spring of 1983. Exactly three months before his death, he presented World News Tonight as chief anchor for the last time.
A few years after Reynolds's passing, musician Paul Hardcastle recorded a section of an ABC documentary about the Vietnam War, that included narration by Reynolds, and later used it as part of his 1985 U.S. Top 40 and U.K. #1 (5 weeks) hit, "19". Hardcastle had a video made of the song that included footage from that documentary that ABC later demanded removed. The ABC footage was later replaced with stock footage, but Reynolds' voice remained on the recording.