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Downs made his first television news broadcast in September 1945 from the still experimental studio of WBKB-TV, a station then owned by the Balaban and Katz theater subsidiary of Paramount Pictures. He became a TV regular, announcing for Hawkins Falls in 1950, the first successful television soap opera, which was sponsored by Lever Brothers Surf detergent. He also announced the Burr Tillstrom children's show Kukla, Fran and Ollie from the NBC studios at Chicago's Merchandise Mart after the network picked up the program from WBKB.

In March, 1954 Downs moved to New York to accept a position as announcer for Pat Weaver's The Home Show starring Arlene Francis. That program lasted until August, 1957. He was the announcer for Sid Caesar's Caesar's Hour for the 1956–57 seasons. Downs became a bona fide television "personality" as Jack Paar's announcer on The Tonight Show from July 1957 until Paar's departure in March, 1962, and then shared hosting until Johnny Carson took over in October 1962. In August 1958 he concurrently began an eleven-year run hosting the original version of the game show Concentration. He hosted NBC's Today Show for nine years from September 1962 to October 1971. He co-hosted the syndicated television program Not for Women Only with Barbara Walters in 1975 and 1976.

Downs earned a postgraduate degree in gerontology from Hunter College while he was hosting Over Easy, a PBS television program about aging that aired from 1977 to 1983.

He was probably best known as the Emmy Award-winning co-anchor (again paired with Walters) of the ABC news TV show 20/20, a primetime news magazine program, from 1978 until his retirement in 1999. His closing tagline "We're in touch, so you be in touch", was written by Brock Brower.

In 1985, he was certified by the Guinness Book of World Records as holding the record for the greatest number of hours on network commercial television (15,188 hours), though he lost the record for most hours on all forms of television to Regis Philbin in 2004.
A published composer himself, Downs hosted the PBS showcase for classical music, Live from Lincoln Center from 1990 to 1996.