Despite the tremendous achievements of existing sensing techniques, sensitive and portable sensing of organophosphorus pesticides (OPs) in a non-polluting manner remains a challenging issue. This work proposed a facile colorimetric paper sensor using γ-MnOOH nanowires (NWs) as a degradable nanozyme and 3,3′,5,5′-tetramethylbenzidine (TMB) as a chromogenic indicator for rapid and sensitive screening of OPs and acetylcholinesterase (AChE) activity. The sensing mechanism was based on the easy disintegration of the oxidase-like γ-MnOOH NWs into invalid Mn2+ ions by the selective reaction with thiocholine (TCh) produced by AChE and acetylthiocholine iodide (ATCh), triggering a remarkable activity loss of MnOOH nanozymes towards TMB oxidation. The concentration of OPs, as an AChE inhibitor, was measured by the changes in absorbance at 652 nm or blue color of oxTMB products. Such detection platform in solution state achieved relatively low limits of detection (LODs) for AChE activity (0.007 mU mL−1), and for two typical OPs, i.e., omethoate (0.35 ng mL−1) and dichlorvos (0.14 ng mL−1), respectively. Further, the portable assembly of such AChE-nanozyme tandem reaction on test paper performed well, reaching LODs of 0.1 mU mL−1 for AChE, 10 ng mL−1 for omethoate, and 3 ng mL−1 for dichlorvos, respectively. Meanwhile, this sensing system showed great selectivity and anti-interfering capacity in both solution and solid states, and worked well in real serum and vegetable samples. The abovementioned results, along with evidence of its good ecological sustainability, demonstrated the superiority of this well-performing platform for application in the food, environmental, and medical fields.