A very compact microstrip reconfigurable filter for fourth-generation (4G) and sub-6 GHz fifth-generation (5G) systems using a new hybrid co-simulation method is presented in this manuscript. The basic microstrip design uses three coupled line resonators with λ/4 open-circuited stubs. The coupling coefficients between the adjacent and non-adjacent resonators are used to tune the filter at the required center frequency to cover the frequency range from 2.5 to 3.8 GHz. The coupling coefficient factors between the adjacent resonators are adjusted to control and achieve the required bandwidth, while the input and output external quality factors are adjusted to ensure maximum power transfer between the input and output ports. Two varactor diodes and biasing circuit components are selected and designed to meet the targeted performance for the tunable filter. The impedance bandwidth is maintained between 95 and 115 MHz with measured return losses of more than 17 dB and measured insertion loss of less than 1 dB. Computer simulation technology (CST) is utilized to design and optimize the presented reconfigurable filter, with hybrid co-simulation technique, using both CST microwave studio (MWS) and CST design studio (DS), is applied to build the model by considering the SPICE representation for the varactor switches and all electronic elements of the biasing circuit. The introduced reconfigurable microstrip filter is also fabricated using a Rogers RO3010 material with a relative dielectric constant of 10.1 and it is printed on a very compact size of 13 × 8 × 0.81 mm3 . An excellent agreement is obtained between the simulation and measurement performance.