In this work, an analog front-end (AFE) circuit for an electrocardiogram (ECG) detection system has been designed, implemented, and investigated in an industry-standard Cadence simulation framework using an advanced technology node of 45 nm. The AFE consists of an instrumentation amplifier, a Butterworth band-pass filter (with fifth-order low-pass and second-order high-pass sections), and a second-order notch filter—all are based on two-stage, Miller-compensated operational transconductance amplifiers (OTA). The OTAs have been designed employing the gm/ID methodology. Both the pre-layout and post-layout simulation are carried out. The layout consumes an area of 0.00628 mm2 without the resistors and capacitors. Analysis of various simulation results are carried out for the proposed AFE. The circuit demonstrates a post-layout bandwidth of 239 Hz, with a variable gain between 44 and 58 dB, a notch depth of −56.4 dB at 50.1 Hz, a total harmonic distortion (THD) of −59.65 dB (less than 1%), an input-referred noise spectral density of <34 μVrms/Hz at the pass-band, a dynamic range of 52.71 dB, and a total power consumption of 10.88 μW with a supply of ±0.6 V. Hence, the AFE exhibits the promise of high-quality signal acquisition capability required for portable ECG detection systems in modern healthcare.