Background: Sedentary behavior (SB) is associated with several chronic diseases and office workers especially are at increased risk. SB is defined by a sitting or reclined body posture with an energy expenditure of ≤1.5 metabolic equivalents. However, current objective methods to measure SB are not consistent with its definition. There is no consensus on which sensor placement and type should be used. Aim: To compare the accuracy of newly developed artificial intelligence models for 15 sensor placements in combination with four signal types (accelerometer only/plus gyroscope and/or magnetometer) to detect posture and physical in-/activity during desk-based activities. Method: Signal features for the model development were extracted from sensor raw data of 30 office workers performing 10 desk-based tasks, each lasting 5 min. Direct observation (posture) and indirect calorimetry (in-/activity) served as the reference criteria. The best classification model for each sensor was identified and compared among the sensor placements, both using Friedman and post hoc Wilcoxon tests (p ≤.05). Results: Posture was most accurately measured with a lower body sensor, while in-/activity was most accurately measured with an upper body or waist sensor. The inclusion of additional signal types improved the posture classification for some placements, while the acceleration signal already contained the relevant signal information for the in-/activity classification. Overall, the thigh accelerometer most accurately classified desk-based SB. Conclusion: This study favors, in line with previous work, the measurement of SB with a thigh-worn accelerometer and adds the information that this sensor is also accurate in measuring physical in-/activity while sitting and standing. © 2020 Human Kinetics, Inc.