RNase R is a conserved exoribonuclease in the RNase II family that primarily participates in RNA decay in all kingdoms of life. RNase R degrades duplex RNA with a 3′ overhang, suggesting that it has RNA unwinding activity in addition to its 3′-to-5′ exoribonuclease activity. However, how RNase R coordinates RNA binding with unwinding to degrade RNA remains elusive. Here, we report the crystal structure of E. coli RNase R at a resolution of 1.85 Å. Structural comparisons with other RNase II family proteins reveal two open RNA-binding channels in RNase R and suggest a tri-helix “wedge” region in the RNB domain that may induce RNA unwinding. We constructed two tri-helix wedge truncation and replacement mutants and they indeed lost their RNA unwinding but not RNA binding or degrading activities. Our results suggest that duplex RNA with overhangs is encircled by the two RNA-binding channels in RNase R. The 3′ overhang is threaded into the active site and the duplex RNA is unwound upon reaching the wedge region during processive RNA degradation at the 3′ end. Thus, RNase R is a proficient enzyme, capable of concurrently binding, unwinding and degrading structured RNA in a highly processive manner during RNA decay.