The use of cover crops in soybean production systems has increased in recent years. There are many questions surrounding cover crops—specifically about benefits to crop production and most effective herbicides for spring termination. No studies evaluating cover crop termination have been conducted across a wide geographic area, to our knowledge. Therefore, field experiments were conducted in 2016 and 2017 in Arkansas, Indiana, Mississippi, Missouri, and Wisconsin for spring termination of regionally specific cover crops. Glyphosate-, glufosinate-, and paraquat-containing treatments were applied between April 15 and April 29 in 2016 and April 10 and April 20 in 2017. Visible control of cover crops was determined 28 days after treatment. Glyphosate-containing herbicide treatments were more effective than paraquat- and glufosinate-containing treatments, providing 71% to 97% control across all site years. Specifically, glyphosate at 1.12 kg ha−1 applied alone or with 2,4-D at 0.56 kg ha−1, saflufenacil at 0.025 kg ha−1, or clethodim at 0.56 kg ha−1 provided the most effective control on all grass cover crop species. Glyphosate-, paraquat-, or glufosinate-containing treatments were generally most effective on broadleaf cover crop species when applied with 2,4-D or dicamba. Results from this research indicate that proper herbicide selection is crucial to successfully terminate cover crops in the spring.